The goal of the present studies will be to investigate the molecular mechanisms regulating release of TSH from the pituitary. A cell perfusion column system will be employed for many of these studies and we will evaluate the combined effects of T3, T4, TRH and changes in ionic medium. For those agents inhibiting TSH release, studies of the nuclear binding of T3 or T4 action has taken place. In addition, the general phenomena of local T4 to T3 conversion will be investigated to determine which of the various tissues in the rat utilize substantial quantities of locally generated T3 intracellularly as the pituitary apparently does. These studies are designed to explore both the mechanism of action and counter-regulatory mechanisms available to the body for rapid alteration in the activating step required for T4 action, namely, its conversion to T3.